Opportunities for targeted therapies: trametinib as a therapeutic approach to canine oral squamous cell carcinomas

Oral tumors are relatively common in dogs, and canine oral squamous cell
carcinoma (COSCC) is the most prevalent oral malignancy of epithelial
origin. COSCC is locally aggressive with up to 20% of patients showing
regional or distant metastasis at the time of diagnosis. The treatment of
choice depends on stage of progression and may include wide surgical
excision, chemotherapy, radiation therapy or any combination thereof.
Although long-term remission is possible, treatments are associated with
significant morbidity and can negatively impact functionality and quality
of life. As a result, many dog owners reject treatment entirely, and some
patients are left with palliative care alone. OSCC tumors have significant
upregulation of the RAS-RAF-MEK-MAPK signaling axis, and we had previously
hypothesized that small-molecule inhibitors that target RAS signaling
might effectively inhibit tumor growth and progression. Here, we
demonstrate that the MEK inhibitor trametinib, an FDA-approved drug for
human cancers, significantly blocks the growth of several aggressive COSCC
cell lines derived from patient tumor samples. Given the limited treatment
options currently available, and the high rate of owner rejection of these
options, these findings provide new hope that more palatable treatment
options may soon enter the veterinary clinic.